| First Author | Cheon Y | Year | 2012 |
| Journal | Biochim Biophys Acta | Volume | 1821 |
| Issue | 9 | Pages | 1278-86 |
| PubMed ID | 22349267 | Mgi Jnum | J:188097 |
| Mgi Id | MGI:5439098 | Doi | 10.1016/j.bbalip.2012.02.003 |
| Citation | Cheon Y, et al. (2012) Disturbed brain phospholipid and docosahexaenoic acid metabolism in calcium-independent phospholipase A(2)-VIA (iPLA(2)beta)-knockout mice. Biochim Biophys Acta 1821(9):1278-86 |
| abstractText | Calcium-independent phospholipase A(2) group VIA (iPLA(2)beta) releases docosahexaenoic acid (DHA) from phospholipids in vitro. Mutations in the iPLA(2)beta gene, PLA2G6, are associated with dystonia-parkinsonism and infantile neuroaxonal dystrophy. To understand the role of iPLA(2)beta in brain, we applied our in vivo kinetic method using radiolabeled DHA in 4 to 5-month-old wild type (iPLA(2)beta(+/+)) and knockout (iPLA(2)beta(-/-)) mice, and measured brain DHA kinetics, lipid concentrations, and expression of PLA(2), cyclooxygenase (COX), and lipoxygenase (LOX) enzymes. Compared to iPLA(2)beta(+/+) mice, iPLA(2)beta(-/-) mice showed decreased rates of incorporation of unesterified DHA from plasma into brain phospholipids, reduced concentrations of several fatty acids (including DHA) esterified in ethanolamine- and serine-glycerophospholipids, and increased lysophospholipid fatty acid concentrations. DHA turnover in brain phospholipids did not differ between genotypes. In iPLA(2)beta(-/-) mice, brain levels of iPLA(2)beta mRNA, protein, and activity were decreased, as was the iPLA(2)gamma (Group VIB PLA(2)) mRNA level, while levels of secretory sPLA(2)-V mRNA, protein, and activity and cytosolic cPLA(2)-IVA mRNA were increased. Levels of COX-1 protein were decreased in brain, while COX-2 protein and mRNA were increased. Levels of 5-, 12-, and 15-LOX proteins did not differ significantly between genotypes. Thus, a genetic iPLA(2)beta deficiency in mice is associated with reduced DHA metabolism, profound changes in lipid-metabolizing enzyme expression (demonstrating lack of redundancy) and of phospholipid fatty acid content of brain (particularly of DHA), which may be relevant to neurologic abnormalities in humans with PLA2G6 mutations. |
